The basic objective of this proposal is to find and study the factor(s) responsible for the increase in sperm motility at the time of ejaculation. Preliminary studies indicate that bovine sperm are quiescent in the epididymis and can be activated to full motility by simple dilution into buffers. A protein of approximately 183,000 daltons appears to reversibly inhibit motility in the epididymis. When epididymal sperm and fluid are diluted by buffer or accessory gland secretions, full motility is induced. This dilution is not accompanied by an increase in cyclic AMP levels. We hypothesize that sperm ATP and cyclic AMP levels are high in caudal sperm in situ and that this inhibitor is responsible for the quiescent state of caudal sperm. Its dilution allows the initiation of motility in these otherwise primed sperm. We plan to purify and characterize this inhibitor, study its interaction with caudal sperm, and determine its biochemical mechanism of action in blocking sperm motility. We will screen numerous possible regulatory systems of sperm motility for an effect on the inhibitor. The detailed action of the inhibitor will be investigated on the selected system. The site of origin of this inhibitor within the epididymis will be determined. The information on the behavior of this system in our model, the bull, will be estended to other species, particularly human and non-human primates. The possible application of this inhibitor to control human fertility will be assessed.